This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. My lab is interested in the DNA damage response (DDR) and cell cycle regulation. Importantly, dysregulation of these pathways has been proven to be a causal factor in cancer progression, and an important determinant of treatment choice and outcome for cancer. Our long-term goal is to delineate the underlying mechanisms of these pathways, and to directly investigate their connection with human cancer. To achieve the goal, we combine in vitro, reconstitutive studies in Xenopus egg extracts with functional investigations in mammalian systems to reveal new insights into these processes. Recent studies revealed a number of Ser/Thr phosphatase complexes involved in DDR regulation. However, little is known about the mechanism and regulation. Interestingly, the DDR phosphatases may be tightly related to cancer, like DDR kinases. We hope to directly assess their cancer involvement through both in vitro and in vivo approaches. Another major interest of our research is the cellular recovery process from DNA damage. Upon completion of DNA repair, the recovery process de-activates the DDR, allowing the cell to return to normal cell cycle progression. This is an important process that determines cell fate post DNA damage or chemotherapy. However, compared to activation of the DDR, the recovery mechanism is less understood. We have developed Xenopus egg extracts as an experimental system to systematically investigate this process.